During studies of the variation in mineral properties in osteoporotic bone, an apparent alteration in the quality of the organic matrix as a function of anatomical location within the same individual was observed. The overall goal of this proposal is to test the hypothesis that there are consistent alterations in the organic matrix of osteoporotic patients compared with normals, which are dependent on the anatomical site, and are due to differences in collagen properties. This will be accomplished through the investigation of three specific aims: Aim 1: To test the hypothesis that there are significant differences in collage/matrix properties between normal and osteoporotic human bones. Furthermore, that these differences are evident in actively bone forming surfaces. This hypothesis will be addressed by comparison of iliac crest biopsies from individuals in whom osteoporosis has been determined based on histologic/histomorphometric parameters, with biopsies from those without morphometric evidence of osteopenia. These studies will be based on histology, and FTIR Imaging (FTIRI) techniques. Aim 2: To test the hypothesis that the observed differences are a function of variations in the biochemical properties of collagen, primarily cross-linking pattern (extent, maturity, origin). This will be verified by a comparison of biochemical and FTIR analyses of a series of highly purified collagen peptides. Additionally. quantitation of the spectroscopic parameters describing collagen cross-links will be achieved utilizing well-established chemical methods to modify predentin. Aim 3: To test the hypothesis that variation in the mechanical properties of bone is dependent part on the quality of the organic matrix. This aim will document the effect of changes in collagen-cross linking pattern observed by FTIRI on the mechanical properties of bone in a well-documented animal model system. Bulk collagen quality will be analyzed by chemical means, and geometric/anatomical variations by FTIRI. These studies will be performed using bones from the beta-aminoproprionitrile rat animal model in which collagen/structure is known to be modified, and for which both geometric and structural properties will be determined. The proposed studies will be based on histology, FTIR Imaging (FTIRI), biomechanical, and biochemical techniques and represent a novel approach to evaluating the organic matrix inosteoporosis.